Temporal and developmental requirements for the Prader-Willi imprinting center

Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3446-50. doi: 10.1073/pnas.1115057109. Epub 2012 Feb 13.


Imprinted gene expression associated with Prader-Willi syndrome (PWS) and Angelman syndrome (AS) is controlled by two imprinting centers (ICs), the PWS-IC and the AS-IC. The PWS-IC operates in cis to activate transcription of genes that are expressed exclusively from the paternal allele. We have created a conditional allele of the PWS-IC to investigate its developmental activity. Deletion of the paternal PWS-IC in the embryo before implantation abolishes expression of the paternal-only genes in the neonatal brain. Surprisingly, deletion of the PWS-IC in early brain progenitors does not affect the subsequent imprinted status of PWS/AS genes in the newborn brain. These results indicate that the PWS-IC functions to protect the paternal epigenotype at the epiblast stage of development but is dispensable thereafter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Blastocyst
  • Brain / embryology
  • DNA Methylation
  • Disease Models, Animal
  • Embryonic Development / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Genomic Imprinting*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neurogenesis / genetics
  • Prader-Willi Syndrome / genetics*
  • Prader-Willi Syndrome / physiopathology
  • Promoter Regions, Genetic / genetics
  • RNA, Small Nucleolar / biosynthesis
  • RNA, Small Nucleolar / genetics
  • Sequence Deletion
  • Time Factors
  • Transcription, Genetic
  • snRNP Core Proteins / biosynthesis
  • snRNP Core Proteins / genetics


  • Nerve Tissue Proteins
  • RNA, Small Nucleolar
  • snRNP Core Proteins